Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts.

Details

Serval ID
serval:BIB_05F924BD2DCA
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Title
Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts.
Journal
Human Genetics
Author(s)
Raghunath M., Superti-Furga A., Godfrey M., Steinmann B.
ISSN
0340-6717 (Print)
ISSN-L
0340-6717
Publication state
Published
Issued date
1993
Volume
90
Number
5
Pages
511-515
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Abnormalities of the microfibrillar protein fibrillin (Fib) have been reported in Marfan syndrome (MFS). The so-called neonatal Marfan syndrome (nMFS) is a lethal phenotype displaying features that are not seen in classical MFS. We have therefore studied the biosynthesis and extracellular deposition of Fib and decorin in fibroblasts from a patient with nMFS and controls. Immunofluorescence of the patient's cell cultures showed an almost complete absence of Fib and a marked reduction of decorin in the extracellular matrix (ECM). The nMFS skin revealed Fib on subbasal microfibrillar bundles in the papillary dermis, and Fib associated with elastic fibers in the reticular dermis; the bundles and fibers were fragmented and thinner than normal. Pulse-chase labeling of cells with [35S]Met/Cys revealed moderately reduced secretion, but a diminished deposition of Fib in the ECM; this was more apparent at a longer chase time. Fib mRNA and synthesis appeared to be normal, whereas both decorin mRNA and biosynthesis were reduced. We therefore assume a structural Fib defect in this patient causing reduced deposition into and/or enhanced removal from the ECM, whereas the reduced decorin biosynthesis may be a secondary regulatory phenomenon. The clinical relevance of this remains unclear. Our findings imply that Fib defects may be responsible for the severe, complex phenotype of nMFS.
Keywords
Blotting, Northern, Decorin, Electrophoresis, Polyacrylamide Gel, Extracellular Matrix/chemistry, Extracellular Matrix/metabolism, Extracellular Matrix Proteins, Fibroblasts/metabolism, Fluorescent Antibody Technique, Humans, Infant, Newborn, Male, Marfan Syndrome/genetics, Marfan Syndrome/metabolism, Microfilament Proteins/analysis, Microfilament Proteins/biosynthesis, Proteoglycans/analysis, Proteoglycans/biosynthesis
Pubmed
Create date
14/03/2011 16:14
Last modification date
20/08/2019 12:28
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